DESCRIPTION: (adapted from the abstract) The main hypothesis of this proposal is that the central nervous system contributes to the increased hypertension when high sodium chloride diets are given. The effect is considered to be due to a decrease in norepinephrine (NE) release from terminals in the anterior hypothalamic area (AHA). The concept is that a decrease of noradrenergic (NA) release in the anterior hypothalamus (AH) earlier mediates a decrease in sympathoinhibition and consequently blood pressure rises. To test this a rat model will be used which is sensitive to the effects of sodium chloride and is spontaneously hypertensive. This is the SHR-S rat. As controls, the SHR-resistant rat and the normotensive WKY rat will be used. The first aim is to test the hypothesis that a decrease in NE release from the AH of SHR-S precedes the development of NaCl-exacerbated hypertension. In a separate experiment NE will be infused chronically into the AHA of rats on a high NaCl diet in an attempt to prevent the appearance of the exacerbated hypertension. The mechanism of the decrease in NE in the AH is hypothesized to be due to a change in baroreflex neurons providing NE to the AHA area or inhibition of any release by neurotransmitters within the AHA. To test this, microdialysis and/or push-pull techniques will be used to provide data for the hypothesis that endogenous atrial natriuretic peptide (ANP) regulates NE release in the AH and secondly, that this peptide is regulated in the SHR-S rat by the NaCl diet. In specific aim 2 the goal of the baroreflex in the NE decrease will be studied. This involves electrophysiological mapping of the AHA neurons which respond to baroreceptor activation. In specific aim 3 the anatomical connections of the AHA which are involved in sympathoinhibitory function will be defined. An attempt will be made to determine whether specific changes of NE axons in the AHA area occur in the SHR-S rat and the percentage of neurons containing NE which send collaterals to the AHA will be measured. With these studies the investigator hopes to determine the mechanism of increased hypertension with sodium diet in sensitive rats.